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To gain new insights into the complex pathophysiology of dilated cardiomyopathy (DCM) we performed a quantitative approach to identify genes with expression patterns that linearly correlate with parameters of cardiac morphology (left ventricular end-diastolic diameter indexed by body surface are (LVEDDI), systolic function [LV ejection fraction (LVEF)], and serum levels of cardiac peptide hormone NH 2 -terminal probrain natriuretic peptide (NT-proBNP) in human endomyocardial biopsies of 47 DCM patients and eight individuals with normal LVEF. A set of genes was identified as common heart failure markers characterized by correlation of their expression with cardiac morphology, systolic function, and NT-proBNP. Among them are already known genes encoding e.g., the natriuretic peptide hormones NPPA and NPPB and its converting enzyme corin, but also potential new heart failure markers like EP300 antisense RNA1 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) along with other genes with so far unknown relation to heart function. In contrast, the expression of other genes including the Ca 2+ flux regulating genes phospholamban (PLN), sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA), and extracellular matrix proteins showed significant correlation with LVEF and LVEDDI only. Those genes seem to reflect more specifically pathological alterations of systolic function and morphology in DCM hearts.

Correlation of gene expression and clinical parameters identifies a set of genes reflecting LV systolic dysfunction and morphological alterations